Data produced by the Laboratory of Tumor Cell Biology indicate that human natural killer cells began de novo expression of the helper/inducer phenotype marker CD4 in response to infection by human herpesvirus (HHV)- 6. Also shown was that the CD4 molecules produced in response to the virus could act as competent receptors for the human pathogen human immunodeficiency virus type 1 (HIV-1), and that productive infection was established in natural killer cells. It was further demonstrated that the receptor for a new HHV (HHV-7) is also CD4, and that HHV-7 and HIV-1 mutually compete for the same cellular ligand. HIV-1 infection of CD4 lymphocytes is significantly diminished in the presence of HHV-7, and the HIV-1 coat protein blocks HHV-7 infection. finally, recent results from experiments investigating the pathogenic mechanisms of acquired immunodeficiency syndrome-associated Kaposi's sarcoma (KS) have demonstrated a pivotal role for basic fibroblast growth factor (bFGF) in the development of KS lesions and the utility of antisense bFGF oligomers and other drugs inhibiting bFGF expression or activity (apolipoprotein-E) as therapeutic agents for KS. Related investigations have also shown that the HIV-1 regulatory protein Tat has pleiotropic effects on normal cells associated with the vascular bed, the milieu from which KS arises. Tat was shown to induce the growth, migration, invasion and adhesion of spindle cells derived from KS (KS cells), believed to be the tumor cells. Other studies demonstrated that the KS cells are of endothelial origin and that inflammatory cytokines increased in HIV-1-infected individuals induce normal endothelial cells to acquire the phenotypic and functional features of KS cells including the spindle cell morphology, the cell responsiveness to Tat, the production and release of bFGF and the induction of KS-like lesions in nude mice. These results indicate that immune stimulation, rather than immunodeficiency is a predisposing factor for KS development and that inflammatory cytokines, bFGF and HIV-1 Tat cooperate to its induction and progression.